Post-traumatic headache

INTRODUCTION — Post-traumatic headache (PTH) is a frequent sequela of traumatic brain injury (TBI). It may also occur as a feature of the postconcussion syndrome symptom complex. After TBI, some patients have short-term acute PTH (<3 months) while PTH is persistent (>3 months duration) in others.

This topic discusses the epidemiology, clinical features, treatment, and prognosis of PTH. Other clinical syndromes related to TBI are discussed separately. (See "Postconcussion syndrome" and "Sequelae of mild traumatic brain injury".)

EPIDEMIOLOGY — PTH is common after traumatic brain injury (TBI) and is the most frequent symptom after mild traumatic brain injury (mTBI) [1]. It is estimated that annually 69 million suffer from TBI worldwide, mostly attributable to mTBI [2]. In a meta-analysis of observational studies that included more than 3100 patients with PTH after TBI, the overall estimated prevalence was 47 percent [3]. Among patients with mTBI, PTH prevalence ranges from 37 to 69 percent in observational studies [4-8], compared with 32 percent reported for patients with moderate to severe TBI from an earlier systemic review [1].

Some patients report short-term PTH symptoms, resolving within three months of TBI [4,5]. Others report chronic PTH symptoms [9]. In one cohort of 1594 patients with mTBI who presented to an emergency department and underwent neuroimaging, acute PTH was reported in 60 percent [8]. Lower rates of chronic PTH were observed at 3, 6, and 12 months, respectively (52 versus 38 versus 29 percent). Other studies have shown that up to 58 percent have PTH at 12 months [4,10]. One study from Norway showed that 0.21 percent of patients with chronic headache had persistent PTH [11], while the lifetime prevalence of PTH was 4.7 percent in males and 2.4 percent in females in a Danish population-based study [12].

The incidence of PTH is primarily based on data from patients seeking immediate medical help at emergency clinics or when admitted to a trauma center. PTH among patients seeking help several days after the trauma, typically via general practitioners, is not well known. Additionally, PTH may be misclassified as migraine or another primary headache syndrome, especially in those with a preexisting history of headaches.

The incidence of persistent PTH is inversely related to the degree of TBI, as PTH is found in 58 percent of patients with mTBI 12 months after the initial injury compared with 33 percent of patients with moderate to severe TBI [13]. Athletes and military personnel with concussion are at risk for PTH, but the incidence in these groups may be underreported [14].

There is little compelling evidence of risk factors for acute or persistent PTH [15]. Several risk factors, however, have been identified in several observational series of patients with PTH [4,5,8,16-18]. These include:

●Age ≤60 years

●Female sex

●Mild (versus moderate or severe) TBI

●History of prior TBI

●History of prior headaches

●Comorbid psychiatric conditions

PATHOPHYSIOLOGY — The underlying cause of PTH is not fully known, but mechanisms related to both migraine and traumatic brain injury (TBI) are implicated. These include impaired descending pain modulation, neurometabolic changes, neuroinflammation, cortical spreading depression, and release of the calcitonin gene-related peptide (CGRP) [19].

The mechanisms that incite and sustain PTH may be more related to neuroinflammation and trigeminal system activation implicated in migraine and other primary headache disorders than those underlying TBI [19]. TBI may cause both immediate effects of brain contusion, cerebral blood vessel damage, and axonal shearing and a secondary cascade of metabolic and cellular excitotoxic and inflammatory changes that can promote development of PTH [20]. The precise relationship between these TBI mechanisms and PTH is not well understood.

The similarities between PTH and migraine are supported by the observation that patients with PTH but no prior history of migraine have been shown to be hypersensitive to CGRP [21]. CGRP is a neuropeptide that may mediate trigeminovascular pain transmission to trigger a migraine attack [22]. CGRP antagonists are a class of medications for acute and preventive treatment of migraine. In study of patients with PTH, 28 percent had a 50 percent reduction in days with moderate or severe headache following an open-label treatment with erenumab, a CGRP receptor antagonist [23].

CLINICAL FEATURES AND DIAGNOSIS

Headache features — PTH symptoms are varied but often resemble the clinical features of primary headache syndromes and can be classified accordingly. Migraine-like and tension-type-like headaches are most common [4,14,24-27]. In most series, tension-type-like headaches are most frequent (75 to 77 percent) [25,26]; however, in others, migraine-type headaches predominate [4,24]. Additionally, among United States soldiers with post-traumatic headaches mainly associated with blast trauma, most were migraine-like [28]. Many patients (27 to 75 percent) have more than one type of headache [26,29]. The headache burden may vary, but in one study of 100 patients with PTH, the mean frequency was 25 days each month [24].

In rare cases, PTH symptoms may be consistent with other primary headaches. These include the trigeminal autonomic cephalgias (such as cluster headache [30], short-lasting unilateral headache with cranial autonomic symptoms [SUNA] [31], and paroxysmal hemicrania [PH] [32]) as well as hemicrania continua [33].

Eliciting whether the headache pattern is migraine-like, tension-type-like, or resembling other headache disorders may help guide symptomatic therapy. (See 'Treatment' below.)

In one study, acute PTH was described most often as having a bilateral localization (56 percent), a moderate or severe intensity (59 percent), and a pressing quality (69 percent) [34].

Multiple triggers and aggravating factors of PTH have been reported. In one study, patients with persistent PTH with migraine-like symptoms reported bright lights lead to aggravation of headache, while those with tension-type-like headache symptoms reported stress and nervousness as headache-aggravating factors [35]. By comparison, another study found that patients with migraine-like headache symptoms reported stress (73 percent), lack of sleep (69 percent), and bright lights (60 percent) as headache-aggravating factors [24].

Associated postconcussive symptoms — Patients with PTH may also have other symptoms of post-concussion syndrome. These may include fatigue, dizziness, sleep difficulties, concentration impairment, and seizures. Depression, anxiety, and insomnia frequently occur after traumatic brain injury (TBI) and PTH [36,37]. In addition, post-traumatic stress disorder may be present in more than 10 percent of patients after TBI [38]. Post-concussive syndrome and other sequelae of TBI are discussed separately. (See "Postconcussion syndrome" and "Sequelae of mild traumatic brain injury".)

Clinical diagnosis — PTH is a clinical diagnosis made in a symptomatic patient who has sustained a TBI and meets diagnostic criteria. PTH is classified according to the International Classification of Headache Disorders (ICHD-3) as being acute or persistent and attributed to either mild TBI (mTBI) or moderate to severe TBI [39]. The key criteria are:

●History of head trauma

●Onset of headache within seven days of trauma

●Headache syndrome not better accounted for by another headache diagnosis

The seven-day interval is somewhat arbitrary but may be useful to help exclude patients with isolated acute headaches who do not subsequently develop PTH. In some series, the onset of PTH after mild TBI has been reported to occur most commonly within 24 hours [40], but other series reported delayed onset by several weeks after mild TBI in some patients [4]. For patients with severe TBI, the seven-day interval may be delayed from the time of the TBI to the time when they regain consciousness and wean from medications that may interfere with the ability to sense or report headache symptoms.

Acute PTH may last up to three months; if longer, symptoms are termed chronic or persistent PTH [39].

There are no imaging or laboratory test findings to identify patients with or without PTH following TBI. Imaging studies or laboratory testing has been used in research settings. Clinical imaging techniques only need to be performed to rule out intracranial hemorrhages, such as parenchymal bleeding, epidural or subdural hemorrhages, and skull fracture. (See 'Testing for alternative causes of headache' below.)

Several imaging and laboratory findings associated with PTH have been found in research settings. Magnetic resonance imaging (MRI) has shown that PTH is associated with abnormalities in brain structure and function [41]. Compared with healthy controls, patients with persistent PTH show reduced cortical thickness in frontal regions and parietal regions compared with controls [42]. Additionally, those with persistent PTH also showed differences in brain volume, surface area, fiber tract integrity, and functional connectivity compared with patients with migraine [43-45]. In another study, patients with an elevated S100 calcium-binding protein B drawn six hours after TBI were likelier to have persistent PTH symptoms at six months than those without [46]. Calcitonin gene-related peptide (CGRP) levels were modestly lower in patients with persistent PTH compared with age- and gender-matched controls [47]. Oxylipins measured within three days of TBI were inversely associated with headache severity three months after the TBI [48].

Additional criteria may be applied to subcategorize patients with PTH according to severity of TBI. All of the following features are absent in PTH attributed to mTBI; if any are present, PTH is attributed to moderate or severe TBI [39]:

●Loss of consciousness for >30 minutes

●Glasgow coma scale (GCS) score <13 (table 1)

●Post-traumatic amnesia or altered level of awareness for more than 24 hours

●Imaging evidence of a TBI (eg, skull fracture, intracranial hemorrhage, or brain contusion)

In addition, PTH attributed to mTBI requires the headache is also associated any of the following symptoms:

●Transient confusion, disorientation, or impaired consciousness

●Loss of memory for events immediately before or after the head injury

●Two or more symptoms of mTBI: nausea, vomiting, visual disturbances, dizziness or vertigo, gait imbalance, or impaired memory or concentration

Testing for alternative causes of headache — PTH is diagnosed clinically. History and examination may be helpful to identify patients with atypical symptoms or neurologic deficits suggestive of alternative diagnoses who warrant diagnostic testing. (See 'Differential diagnosis' below.)

●Neuroimaging – Many patients with PTH will have had diagnostic neuroimaging with head computed tomography (CT) or magnetic resonance imaging (MRI) during the acute evaluation of the TBI. In other patients and patients whose symptoms or examination has worsened since acute imaging, we prefer brain MRI with gadolinium contrast if feasible. Additionally, CT or MR angiography of the head and neck are performed when carotid or vertebral artery dissection are suspected.

●Other testing – Other diagnostic testing such as electroencephalogram (EEG) or lumbar puncture is reserved for patients with atypical symptoms or abnormal exam findings suggestive of alternate diagnoses.

Differential diagnosis — Several other headache syndromes may occur after TBI. The specific headache symptoms and associated neurologic findings may help to discriminate from PTH.

●Intracranial hypotension (IH) – Headache may develop due to IH, which could be due to a dural tear. Symptoms favoring IH include onset of headache when sitting upright and resolution after lying horizontally [49]. (See "Spontaneous intracranial hypotension: Pathophysiology, clinical features, and diagnosis".)

●Subdural hematoma (SDH) – Persistent headache following a head trauma could be due to acute or chronic SDH. Patients may or may not have associated focal neurologic deficits. SDH is more common in the older adult population [50]. (See "Subdural hematoma in adults: Etiology, clinical features, and diagnosis".)

●Occipital neuralgia – Injury to the head may also lead to traumatic neuralgias such as occipital neuralgia in which there is a usual one-sided paroxysmal, shooting, or stabbing pain in the posterior part of the head. This neuralgia is located in the distributions of the greater, lesser, and/or third occipital nerve and can be accompanied by tenderness and/or diminished sensation or dysesthesia in the affected area [51]. (See "Occipital neuralgia".)

●Trigeminal neuropathy – TBI could also lead to trigeminal neuropathy, with either positive (hyperalgesia, allodynia) or negative (hypoesthesia, hypoalgesia) signs of nerve dysfunction [51]. (See "Overview of craniofacial pain", section on 'Painful trigeminal neuropathy'.)

●Cervical artery dissection – Carotid or vertebral artery dissection can lead to headache, most often accompanied by ipsilateral neck and head or periorbital pain. Neurologic deficits associated with carotid artery dissection may include Horner's syndrome (ipsilateral ptosis, miosis, anhidrosis). Carotid or vertebral artery dissection may also cause acute ischemic stroke. (See "Cerebral and cervical artery dissection: Clinical features and diagnosis".)

●Temporomandibular joint (TMJ) disorders – TMJ may occur after TBI involving facial structures. Patients may report jaw pain and/or hemicranial headaches. (See "Temporomandibular disorders in adults".)

●Premorbid headache syndromes – When a preexisting primary headache increases twofold or greater in frequency and/or severity in close temporal relation to a traumatic event, both the primary and the secondary headache diagnoses should be given [39]. As an example, patients with migraine whose symptoms worsen twofold within seven days after TBI would be classified as having migraine and (migraine-like) PTH. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults" and "Tension-type headache in adults: Etiology, clinical features, and diagnosis".)

●Medication overuse headache (MOH) – Patients with a preexisting headache disorder who regularly take medications for symptomatic management of a headache occurring more than 15 days per month for at least 3 months may have MOH. Patients who meet diagnostic criteria for PTH and MOH are given both diagnoses. (See "Medication overuse headache: Etiology, clinical features, and diagnosis".)

TREATMENT — Despite being one of the most frequent secondary headache syndromes, there are no evidence-based treatment strategies for PTH. Treatment should not only focus on ameliorating headache symptoms but also other related symptoms if present, including those from postconcussion syndrome, which most frequently accompanies PTH. (See 'Associated postconcussive symptoms' above and "Postconcussion syndrome".)

Treatment approach — For patients with PTH, we start medications typically used to treat other primary headache syndromes. (See 'Initial medication options' below.)

A systematic review of both acute and preventive pharmacologic treatment of PTH was limited to studies using an open-label design, those with investigator-subject interaction, and those with a high placebo response [52]. In the absence of evidence-based options, we suggest that treatment should be tailored to the headache pattern that the specific PTH resembles [14]. Thus, PTH treatment may follow the recommendations of migraine or tension-type headache. (See "Acute treatment of migraine in adults" and "Preventive treatment of episodic migraine in adults" and "Tension-type headache in adults: Acute treatment" and "Tension-type headache in adults: Preventive treatment".)

Initial medication options — Although many patients with PTH may be treated according to the pattern of their headaches, we tailor our initial medication selection to patient comorbidities and medication risk-benefit profiles.

Acute treatment — For patients with acute PTH or those with persistent PTH with infrequent attacks, acute treatment may manage symptoms and limit exposure to adverse drug effects.

●Initial treatment options – We typically start with a simple analgesic medication like ibuprofen at 400 to 800 mg up to three times daily. As an alternative, acetaminophen (paracetamol) at 500 to 1000 mg up to three times daily may be used. Analgesics to treat headaches are discussed in further detail separately. (See "Acute treatment of migraine in adults", section on 'Simple analgesics' and "Tension-type headache in adults: Acute treatment", section on 'Simple analgesics for most patients'.)

For patients unresponsive to simple analgesics for acute therapy, we typically use a combination analgesic medication also containing caffeine before starting preventive therapy. (See "Tension-type headache in adults: Acute treatment", section on 'Combination analgesics with caffeine' and 'Preventive treatments' below.)

For patients with acute PTH and frequent attacks inadequately responsive to acute treatments and for patients with persistent PTH (>3-month duration), we start a preventive medication. (See 'Preventive treatments' below.)

●Patients with nausea – Nausea accompanying the headache can be treated with antiemetics (eg, metoclopramide or prochlorperazine). The role of antiemetics to treat headaches is discussed in greater detail separately. (See "Acute treatment of migraine in adults", section on 'Antiemetics'.)

●Alternative options – For other patients with migraine-like headache symptoms who do not respond to simple analgesics or analgesic medications combined with caffeine, alternative acute treatment options include:

•Triptans

•Triptans combined with nonsteroidal anti-inflammatory drugs (NSAIDs)

•Calcitonin gene-related peptide (CGRP) ligand-receptor antagonists

•Dihydroergotamine-ergotamine alone or with caffeine

These approaches are discussed in further detail separately. (See "Acute treatment of migraine in adults", section on 'Triptans' and "Acute treatment of migraine in adults", section on 'Triptans with NSAIDs' and "Acute treatment of migraine in adults", section on 'CGRP antagonists' and "Acute treatment of migraine in adults", section on 'Ergots'.)

Preventive treatments — For patients with persistent PTH and those with acute PTH and frequent attacks inadequately responsive to acute treatments, we start a preventive medication. The threshold to start a preventive medication is guided by the severity of symptoms and patient preference but may include those who have headache duration longer than 12 hours or have at least four monthly headache days.

●For patients with PTH where migraine-type headaches predominate, we prefer an antihypertensive medication such as metoprolol or candesartan. For those unresponsive to or unable to tolerate an antihypertensive or in patients with comorbid depression or neuropathic pain, we use amitriptyline. Other medications used to prevent migraine are reasonable alternatives. (See "Preventive treatment of episodic migraine in adults".)

•Metoprolol is started at 50 mg daily and after one week may be increased to 100 mg. After one to two months, the dose may be increased by 50 mg weekly, if tolerated, up to 200 mg daily.

•Candesartan is started at 8 mg daily and after one week may be increased to 16 mg. The dose may be increased by 8 mg weekly, if tolerated, up to 32 mg. We measure serum electrolytes and supine blood pressure to evaluate for hyperkalemia, deterioration of renal function, or hypotension before treatment and when increasing the daily dosage of candesartan.

•Amitriptyline can be started at 10 mg at bedtime and increased by 10 mg weekly, if tolerated, up to 100 mg at bedtime. We obtain an electrocardiogram to evaluate for arrhythmias before treatment and when the dose exceeds 40 mg daily.

●For patients with PTH where tension-type headaches predominate, we prefer amitriptyline, mirtazapine, or venlafaxine. Other medications used to prevent tension-type headaches are reasonable alternatives. (See "Tension-type headache in adults: Preventive treatment".)

•Amitriptyline dosing is the same as for those with migraine-type headaches, discussed immediately above.

•Mirtazapine is started at 15 mg at bedtime. The dose can be increased to 30 mg after one week. We obtain an electrocardiogram to evaluate for arrhythmias before treatment and when increasing the daily dosage.

•Venlafaxine is started at 75 mg at bedtime. The dose can be increased to 150 mg after one week. We obtain an electrocardiogram to evaluate for arrhythmias before treatment and when increasing the daily dosage.

●For the rare patient with clinical features of PTH that are neither migraine-type nor tension-type in character, we use the same preventive medication and dosing regimens as for patients with the primary headache syndromes to which the headaches resemble.

●For patients with PTH and medication overuse headache, we discontinue the overused medication and start a preventive medication. (See "Medication overuse headache: Treatment and prognosis".)

However, it is important to be aware that this approach lacks evidence and the efficacy has, when reported, been poor [53]. In addition, side effects to pharmacologic treatment may conflict with PTH comorbidities such as post-traumatic stress disorder, depression, and anxiety. Additionally, medication overuse headache is also very frequent among patients with PTH. As an example, among 167 participants with mild traumatic brain injury (mTBI), who prospectively reported new or worse headache at 3, 6, or 12 months, more than 70 percent used over-the-counter medication to treat headache [54]. Furthermore, in a study of 77 adolescents with concussion and persistent PTH, 70 percent met criteria for probable medication-overuse headache [55]. After discontinuing analgesics, 69 percent reported resolution of headaches or improvement to pre-concussion headache patterns [55].

Alternative therapeutic options — As there is no high-quality evidence to support a pharmacologic agent to treat PTH, some patients may prefer nonpharmacologic treatment options. Such options are included in a guideline for concussion/mTBI and persistent symptoms from the Ontario Neurotrauma Foundation [56]. Nonpharmacologic options include:

●Physical or manual therapies [57]

●Exercise [58]

●Avoidance of headache triggers [59]

●Progressive muscle relaxation [60]

●Sleep hygiene education [61]

●Dietary and environment modifications [59]

●Cognitive behavioral therapy [57,62]

PROGNOSIS — Some patients with acute PTH do not develop persistent PTH, as headaches may resolve spontaneously or with treatment within three months of the traumatic brain injury (TBI). In one study of 397 children with TBI, recovery was slower when PTH had migraine-like features [63]. However, the natural history of PTH is not well described, and prognostic data on patients with PTH are sparse.

Some insight into the prognosis of PTH may be found from patients with PTH as a component of neuropsychiatric symptoms after TBI. Most patients with postconcussion syndrome typically recover within 3 to 12 months [64]. However, for others, PTH may be chronic. In one study of 110 patients with mild TBI (mTBI), 76 percent reported headaches at one month and 58 percent reported persisting PTH at a mean follow up of 98 days [65]. In another study, only 30 percent of 116 patients with PTH reported headache resolution by 24 months after TBI [66]. The persistence of PTH for some patients after TBI may reflect secondary chronic post-inflammatory and metabolic changes related to migrainous pathophysiology, but further study is required to clarify these issues [19].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Increased intracranial pressure and moderate-to-severe traumatic brain injury".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Postconcussion syndrome (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition and clinical setting – Post-traumatic headache (PTH) is a frequent sequela of traumatic brain injury (TBI). It may also occur as a feature of the postconcussion syndrome symptom complex. (See 'Introduction' above and 'Epidemiology' above.)

●Clinical features – PTH symptoms are varied but can be classified similarly to primary headache syndromes to which the clinical features resemble. Migraine-like and tension-type-like headaches are most common. (See 'Headache features' above.)

●Diagnosis – PTH is a clinical diagnosis made in a symptomatic patient with an onset of headache within seven days after a TBI when the headache syndrome is not better accounted for by another headache diagnosis. Acute PTH may last up to three months; if longer, symptoms are termed chronic or persistent PTH. (See 'Clinical diagnosis' above.)

●Treatment approach – For patients with PTH, we start medications typically used to treat other primary headache syndromes and tailor our initial medication selection to patient comorbidities and medication risk-benefit profiles. (See 'Treatment' above.)

•Acute treatment – For patients with acute PTH or those with persistent PTH with infrequent attacks, acute treatment may manage symptoms and limit exposure to adverse effects of medications. For most patients, we suggest initial treatment with a simple analgesic medication like ibuprofen or acetaminophen (paracetamol) (Grade 2C). For patients with symptoms unresponsive to simple analgesics, we use combination analgesics or abortive therapies commonly used for migraine headaches including triptans, calcitonin gene-related peptide (CGRP) antagonists, or dihydroergotamine-ergotamine. (See 'Acute treatment' above.)

•Preventive treatment – For patients with persistent PTH and those with acute PTH and frequent attacks inadequately responsive to acute treatments, we start a preventive medication.

-For patients with PTH where migraine-type headaches predominate, we suggest an antihypertensive medication such as metoprolol or candesartan (Grade 2C). For those unresponsive to or unable to tolerate an antihypertensive or in patients with comorbid depression or neuropathic pain, we suggest amitriptyline (Grade 2C). Other medications used to prevent migraine are reasonable alternatives.

-For patients with PTH where tension-type headaches predominate, we suggest amitriptyline, mirtazapine, or venlafaxine (Grade 2C). Other medications used to prevent tension-type headaches are reasonable alternatives.

●Prognosis – Some patients with acute PTH do not develop persistent PTH, as headaches may resolve spontaneously or with treatment. However, for others, PTH may become chronic. The natural history of PTH is not well described, and prognostic data on patients with PTH are sparse. (See 'Prognosis' above.)